We investigated Contrast enhancing lesions (CELs) on MRI in 16 multiple sclerosis (MS) patients. Based upon shape, CELs may be defined as nodular (nCEL) or ring (rCEL) lesions. Several short-term studies pointed towards the assumption that rCELs represent areas of a more aggressive inflammatory process. A 2 year retrospective study we examined monthly MRI to follow rCEL and nCELs evolution during the natural history. New CELs were identified monthly on month 4-9 MRIs, using month 1-3 MRIs to ensure that all CELs were not previously enhancing. Chronic black holes (cBHs) on T1w images were counted monthly upon CEL disappearance up to the 24th MRI. Fifty-two new rCELs and 281 nCELs were identified. rCELs had larger mean (p <0.0001) volumes than nCELs. The proportion of cBHs from rCELs was similar (p = 0.0710) to the proportion of cBHs from nCELs. Likewise, the length of persistence of cBHs deriving from rCELs was similar (p = 0.1262) to the duration of cBHs from nCELs.These results suggest that the radiologic characteristics associated with the acute phase of ring contrast-enhancing lesions and nodular contrast-enhancing lesions do not necessarily reflect a poorer lesion outcome over time. We also investigated the heterogeneity in MRI patterns of response to interferon beta across MS patients or within an individual patient over time. 15 patients with relapsing-remitting multiple sclerosis underwent monthly MRIs and clinical examinations (6-month pretherapy phase and 36-month therapy phase) and bimonthly neutralizing antibody tests. On each MRI, the total number of CELs was noted. Therapy MRI responders were defined as those with a reduction of 60% or more in the total number of contrast-enhancing lesions during each semester of therapy. Eight patients (53.3%) were MRI responders and 7 (46.7%) were nonresponders. Of those 7, 3 (20.0%) had only an initial optimal reduction of the total number of contrast-enhancing lesions, 2 (13.3%) never reached an optimal response, and 2 (13.3%) had a delayed optimal response. No clear association between neutralizing antibody profile and MRI response was evident. We concluded that serial MRI evaluations disclose that approximately only half of the patients treated with interferon beta achieve and maintain a full response to the drug over time, although an additional small number of individuals may still restore an optimal response to the drug after an initial failure.